Abstract P249: Central Nervous System Control of Plasma Aldosterone and Endogenous Ouabain in Angiotensin II-Salt Hypertension

High salt intake markedly enhances hypertension induced by Ang II. We evaluated peripheral mechanisms which may amplify central mechanisms activated by Ang II-salt. In the 1st exp, Wistar rats were sc infused with Ang II at low dose of 150 ng/kg/min together with 2% high salt diet for 14 days. In the 2nd exp, MR blockers (eplerenone, spironolactone), ENaC blocker (benzamil), AT1R blocker (losartan) or vehicles (Veh) were icv infused combined with Ang II-salt. BP was recorded by telemetry. Plasma corticosterone (Cor), aldosterone (aldo) and endogenous ouabain (EO) were measured by RIA. Gene expression was assessed by real-time qPCR. Ang II alone caused a small increase in MAP (112±1 vs. 99±1 mmHg), but BP was markedly increased by Ang II-salt (152±4 mmHg, Pu003c0.05 vs. others). BP increases to Ang II-salt were largely inhibited by central infusion of MR blockers, benzamil or losartan. Only Ang II together with salt increased plasma aldo, Cor and EO. In the adrenal cortex, both Ang II alone and Ang II-salt increased CYP11B2 expression but neither affected CYP11B1, Hsd3b1 or AT1R mRNA expression. Central blockades significantly (pu003c0.05) lowered plasma aldo and EO in rats on Ang II-salt. Central blockades had no effect on Hsd3b1, CYP11B1 and AT1R mRNA but markedly decreased Ang II-salt induced CYP11B2 expression in the adrenal cortex. Together, these results suggest that in Ang II-salt hypertension, Ang II-AT1R signaling and MR-ENaC pathway in the brain increase plasma aldo and EO, which may amplify BP responses to central mechanisms and contribute to severe hypertension by Ang II-salt vs Ang II alone. ![][1] [1]: /embed/graphic-1.gif